Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
J Am Chem Soc. 2009 Dec 9;131(48):17536-7. doi: 10.1021/ja907055q.
Lysine specific demethylase 1 (LSD1) plays a key role in the regulation of gene expression by removing the methyl groups from methylated Lys4 of histone H3 (H3K4). Here we report the identification of the first small-molecule LSD1-selective inhibitors. These inhibitors show in vivo H3K4-methylating activity and antiproliferative activity and should be useful as lead structures for anticancer drugs and as tools for studying the biological roles of LSD1.
赖氨酸特异性去甲基化酶 1（LSD1）通过去除组蛋白 H3 赖氨酸 4（H3K4）上的甲基基团，在基因表达调控中发挥关键作用。在此，我们报告了首个小分子 LSD1 选择性抑制剂的鉴定。这些抑制剂在体内显示出 H3K4 甲基化活性和抗增殖活性，可用作抗癌药物的先导结构，并可作为研究 LSD1 生物学功能的工具。
